PURPOSE: Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free survival (PFS), and objective response rate (ORR) results. METHODS: nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination with tamoxifen in women with endocrine-refractory HR + , HER2- MBC previously treated with chemotherapy. Patients were randomized 1:1:1 to: abemaciclib 150 mg and tamoxifen 20 mg (A + T), abemaciclib 150 mg (A-150), or abemaciclib 200 mg and prophylactic loperamide (A-200). OS was the main prespecified secondary endpoint. PFS, ORR, and safety at 24 months were compared to previously reported primary analysis results. RESULTS: Of the 234 patients enrolled, 12 were receiving study treatment at data cutoff (28Jun2019). Median follow-up was 27.2 months. Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03 and A-150 versus A-200: HR 0.96; 95%CI [0.64, 1.44], P = 0.83). PFS and ORR results at 24 months were consistent with the primary analysis. The safety profile corresponded with previous reports. CONCLUSION: The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2- MBC, as well as the previously reported primary PFS and ORR results, with no new safety signals observed. Trial Registration ClinicalTrials.gov Identifier: NCT02747004.

Breast and Gynecologic Research Program Sarah Cannon Research Institute Tennessee Oncology PLLC 250 25th Ave North Suite 200 Nashville TN 37203 USA

Breast Center Cantonal Hospital St Gallen Switzerland

Breast Center University of Ulm Ulm Germany

Centre Hospitalier Universitaire Liège and Liège University Liège Belgium

Centro de Referência da Saúde da Mulher Hospital Pérola Byington FMUSP São Paulo Brazil

Chang Gung Memorial Hospital Chang Gung University Linkou Taoyuan City Taiwan

City Clinical Oncology Center St Petersburg Russia

Department of Medical Oncology Baskent University Adana Turkey

Eli Lilly and Company Indianapolis IN USA

Faculty of Biomedical and Health Sciences Department of Medicine Universidad Europea de Madrid Madrid Spain

Instituto de Investigación Sanitaria Gregorio Marañón Universidad Complutense CIBERONC GEICAM Madrid Spain

International Breast Cancer Center Quironsalud Group Barcelona Spain

Masarykuv Onkologický Ustav Brno Czech Republic

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ClinicalTrials.gov
NCT02747004